The focus of this project is to identify genes that are important in the normal development of the inner ear. The inner ear undergoes elaborate morphological changes during development. Perturbation of this developmental process very often leads to functional deficits. A good knowledge of the molecular basis that underlies the morphological events occurring during normal inner ear development will facilitate the understanding of deficits resulting from genetic defects. We found that BMP4 (bone morphogenetic protein) is an early marker for all the sensory organs of the chick inner ear. Using BMP4 cDNA as well as two other markers: Msx-1 (muscle segment homeobox) and p75NGFR (nerve growth factor receptor), the origin and time of generation of each presumptive sensory organ in the chick inner ear was determined. In addition, the gene expression patterns of BMP4 and 7 during sensory organ maturation were different in the vestibular and auditory systems. Bone morphogenetic proteins may be important in the induction as well as differentiation of sensory organs in the chick inner ear. These hypotheses are currently under investigation using avian retroviral vectors for gain or loss of function of BMP4 during inner ear development. Furthermore, our results, taken together with those of others, suggest that the inner ear is molecularly defined early in development. To test the consequences when such an intricate gene expression pattern is disturbed, exogenous retinoic acid was used as a perturbant. Implantation of beads soaked with retinoic acid into otocysts at embryonic day 2.5 showed a dose-dependent effect of retinoic acid on the normal morphogenesis of the inner ear. The phenotypes obtained ranges from inner ears with only the superior semi-circular canal affected to the most severe cases with malformation in all three semi-circular canals and the cochlea. The mechanism(s) whereby retinoic acid mediates these effects is currently under investigation.